1,3-Bis[(3-chloro­pyrazin-2-yl)­oxy]benzene

Abstract

The asymmetric unit of the title compound, C₁₄H₈Cl₂N₄O₂, contains one half-mol­ecule, the complete mol­ecule being generated by the operation of a twofold rotation axis. The Cl atom deviates significantly from the plane of the pyrazine ring [0.0215 (4) Å]. The central benzene ring makes a dihedral angle of 72.82 (7)° with the plane of the pyrazine ring.

Related literature  

For applications of the pyrazine ring system in drug development, see: Du et al. (2009 ▶); Dubinina et al. (2006 ▶); Ellsworth et al. (2007 ▶); Mukaiyama et al. (2007 ▶). For background to the fluorescence properties of compounds related to the title compound, see: Kawai et al. (2001 ▶); Abdullah (2005 ▶). For a related structure, see: Nasir et al. (2010 ▶).

Experimental  

Crystal data  

• C₁₄H₈Cl₂N₄O₂

• M _r = 335.14

• Monoclinic,

• a = 9.9618 (3) Å

• b = 10.2196 (4) Å

• c = 14.6010 (6) Å

• β = 106.231 (2)°

• V = 1427.22 (9) ų

• Z = 4

• Mo Kα radiation

• μ = 0.47 mm⁻¹

• T = 293 K

• 0.30 × 0.25 × 0.20 mm

Data collection  

• Bruker SMART APEXII area-detector diffractometer

• Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.873, T _max = 0.912

• 6736 measured reflections

• 1781 independent reflections

• 1552 reflections with I > 2σ(I)

• R _int = 0.026

Refinement  

• R[F ² > 2σ(F ²)] = 0.036

• wR(F ²) = 0.113

• S = 1.00

• 1781 reflections

• 101 parameters

• H-atom parameters constrained

• Δρ_max = 0.25 e Å⁻³

• Δρ_min = −0.31 e Å⁻³

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT (Bruker, 2008 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▶) and Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: SHELXL97and PLATON (Spek, 2009 ▶).

Supplementary Material

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

supplementary crystallographic information

Comment

The pyrazine ring system is a useful structural element in medicinal chemistry and has found broad applications in drug development which can be used as antiproliferative agent (Dubinina et al., 2006), potent CXCR3 antagonists (Du et al., 2009), CB1 antagonists (Ellsworth et al., 2007), and c-Src inhibitory (Mukaiyama et al., 2007). On-going structural studies of heterocyclic N-containing derivatives (Nasir et al., 2010) are motivated by an investigation of their fluorescence properties (Kawai et al., 2001; Abdullah, 2005). In view of different applications of this class of compounds, we have undertaken the single crystal structure determination of the title compound.

The title compound C₁₄ H₈ Cl₂ N₄ O₂, contains a half of the molecule in an asymmetric unit; the complete molecule is generated by two the fold rotation axis along the direction [0 1 0] with the symmetry code: -x, y, -z+1/2. X-ray analysis confirms the molecular structure and atom connectivity of the compound (Fig. 1). The deviation of the atom Cl1 from the pyrazine ring (C1/N1/C2/C3/N2/C4) is -0.0215 (4) Å.

The central phenyl ring (C5/C6/C7/C8/C5ⁱ/C7ⁱ) forms the dihedral angle of 72.82 (7) ° with the pyrazine ring (C1/N1/C2/C3/N2/C4). The dihedral angle between the pyrazine rings (C1/N1/C2/C3/N2/C4) and (C1ⁱ/N1ⁱ/C2ⁱ/C3ⁱ/N2ⁱ/C4ⁱ) is 68.38 (3) ° (Macrae et al., 2008). The crystal packing is via van der Waals interactions, only.

Experimental

To a stirred solution of Cs₂CO₃/K₂CO₃ (22 mmol) in CH₃CN (50 mL), resorcinol (10 mmol) was added and stirred for 5 min. 2,3-dichloropyrazine (20 mmol) in CH₃CN (100 mL) was added dropwise to the above reaction mixture and allowed for stirring at refluxing condition for 12 h. After the reaction was complete, the reaction mixture was allowed to attain room temperature and then evaporated to dryness. The residue obtained was extracted with CH₂Cl₂ (3 x 100 mL), washed with water (3 x 100 mL), brine and then dried over Na₂SO₄. Evaporation of the organic layer gave a residue, which on purification using column chromatography with hexane/CHCl₃ (1:1) as an eluent gave the corresponding compound. Single crystals suitable for X-ray diffraction were obtained by slow evaporation of a solution of the title compound in hexane at room temperature.

Refinement

The hydrogen atoms were placed in calculated positions with C—H = 0.93 Å, refined in the riding model with fixed isotropic displacement parameters:U_iso(H) = 1.2U_eq(C).

Figures

Fig. 1.

The molecular structure of the title compound, showing displacement ellipsoids drawn at the 30% probability level. H atoms are presented as small spheres of arbitrary radius. The related atoms have the symmetry code: (a) -x, y, -z+1/2.

Crystal data

C14H8Cl2N4O2	F(000) = 680
Mr = 335.14	Dx = 1.560 Mg m−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2yc	Cell parameters from 1781 reflections
a = 9.9618 (3) Å	θ = 2.9–28.4°
b = 10.2196 (4) Å	µ = 0.47 mm−1
c = 14.6010 (6) Å	T = 293 K
β = 106.231 (2)°	Block, colourless
V = 1427.22 (9) Å3	0.30 × 0.25 × 0.20 mm
Z = 4

Data collection

Bruker SMART APEXII area-detector diffractometer	1781 independent reflections
Radiation source: fine-focus sealed tube	1552 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.026
ω and φ scans	θmax = 28.4°, θmin = 2.9°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −13→13
Tmin = 0.873, Tmax = 0.912	k = −13→12
6736 measured reflections	l = −19→14

Refinement

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.036	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.113	H-atom parameters constrained
S = 1.00	w = 1/[σ2(Fo2) + (0.0685P)2 + 0.5533P] where P = (Fo2 + 2Fc2)/3
1781 reflections	(Δ/σ)max < 0.001
101 parameters	Δρmax = 0.25 e Å−3
0 restraints	Δρmin = −0.31 e Å−3

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	0.10770 (15)	0.37514 (13)	−0.02670 (10)	0.0461 (3)
C2	−0.07466 (18)	0.3213 (2)	−0.15100 (11)	0.0644 (4)
H2	−0.1203	0.3246	−0.2159	0.077*
C3	−0.13428 (17)	0.25363 (19)	−0.09216 (11)	0.0618 (4)
H3	−0.2196	0.2121	−0.1178	0.074*
C4	0.04654 (14)	0.30517 (13)	0.03426 (9)	0.0417 (3)
C5	0.05477 (14)	0.23121 (15)	0.18814 (9)	0.0454 (3)
C6	0.0000	0.3013 (2)	0.2500	0.0436 (4)
H6	0.0000	0.3923	0.2500	0.052*
C7	0.05777 (19)	0.09686 (17)	0.18801 (10)	0.0597 (4)
H7	0.0979	0.0516	0.1470	0.072*
C8	0.0000	0.0305 (2)	0.2500	0.0694 (7)
H8	0.0000	−0.0605	0.2500	0.083*
N1	0.04795 (16)	0.38337 (13)	−0.11809 (9)	0.0580 (3)
N2	−0.07257 (13)	0.24545 (13)	0.00221 (8)	0.0515 (3)
O1	0.11655 (11)	0.30189 (12)	0.12853 (7)	0.0537 (3)
Cl1	0.26460 (5)	0.45456 (4)	0.01959 (4)	0.06883 (19)

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
C1	0.0581 (7)	0.0383 (6)	0.0511 (8)	0.0030 (5)	0.0308 (6)	−0.0006 (5)
C2	0.0681 (10)	0.0875 (12)	0.0390 (7)	0.0107 (9)	0.0175 (7)	0.0107 (7)
C3	0.0527 (8)	0.0885 (12)	0.0432 (8)	−0.0002 (8)	0.0121 (6)	0.0067 (7)
C4	0.0491 (6)	0.0447 (7)	0.0363 (6)	0.0042 (5)	0.0201 (5)	0.0004 (5)
C5	0.0493 (7)	0.0565 (8)	0.0298 (6)	−0.0035 (5)	0.0104 (5)	0.0000 (5)
C6	0.0461 (9)	0.0492 (10)	0.0340 (8)	0.000	0.0085 (7)	0.000
C7	0.0861 (11)	0.0587 (9)	0.0385 (7)	0.0055 (8)	0.0240 (7)	−0.0053 (6)
C8	0.119 (2)	0.0472 (12)	0.0468 (12)	0.000	0.0308 (13)	0.000
N1	0.0756 (8)	0.0596 (8)	0.0484 (7)	0.0084 (6)	0.0332 (6)	0.0117 (6)
N2	0.0489 (6)	0.0689 (8)	0.0387 (6)	−0.0036 (5)	0.0157 (5)	0.0063 (5)
O1	0.0553 (6)	0.0703 (7)	0.0374 (5)	−0.0130 (5)	0.0162 (4)	−0.0022 (4)
Cl1	0.0778 (3)	0.0608 (3)	0.0815 (4)	−0.02286 (19)	0.0447 (2)	−0.01437 (19)

Geometric parameters (Å, º)

C1—N1	1.303 (2)	C5—C7	1.373 (2)
C1—C4	1.4064 (18)	C5—C6	1.3789 (17)
C1—Cl1	1.7229 (15)	C5—O1	1.3991 (17)
C2—N1	1.340 (2)	C6—C5i	1.3789 (17)
C2—C3	1.362 (2)	C6—H6	0.9300
C2—H2	0.9300	C7—C8	1.379 (2)
C3—N2	1.345 (2)	C7—H7	0.9300
C3—H3	0.9300	C8—C7i	1.379 (2)
C4—N2	1.2996 (18)	C8—H8	0.9300
C4—O1	1.3584 (16)
N1—C1—C4	121.76 (14)	C6—C5—O1	117.57 (14)
N1—C1—Cl1	118.42 (11)	C5—C6—C5i	117.45 (19)
C4—C1—Cl1	119.81 (11)	C5—C6—H6	121.3
N1—C2—C3	121.90 (14)	C5i—C6—H6	121.3
N1—C2—H2	119.0	C5—C7—C8	118.51 (15)
C3—C2—H2	119.0	C5—C7—H7	120.7
N2—C3—C2	121.51 (15)	C8—C7—H7	120.7
N2—C3—H3	119.2	C7i—C8—C7	121.1 (2)
C2—C3—H3	119.2	C7i—C8—H8	119.4
N2—C4—O1	120.78 (11)	C7—C8—H8	119.4
N2—C4—C1	121.62 (12)	C1—N1—C2	116.50 (13)
O1—C4—C1	117.60 (12)	C4—N2—C3	116.71 (13)
C7—C5—C6	122.18 (14)	C4—O1—C5	116.90 (10)
C7—C5—O1	120.12 (13)
N1—C2—C3—N2	−0.1 (3)	C4—C1—N1—C2	−0.2 (2)
N1—C1—C4—N2	0.0 (2)	Cl1—C1—N1—C2	−179.30 (12)
Cl1—C1—C4—N2	179.08 (11)	C3—C2—N1—C1	0.3 (3)
N1—C1—C4—O1	179.94 (13)	O1—C4—N2—C3	−179.81 (14)
Cl1—C1—C4—O1	−0.95 (17)	C1—C4—N2—C3	0.2 (2)
C7—C5—C6—C5i	−1.04 (11)	C2—C3—N2—C4	−0.1 (3)
O1—C5—C6—C5i	−176.94 (13)	N2—C4—O1—C5	0.4 (2)
C6—C5—C7—C8	2.0 (2)	C1—C4—O1—C5	−179.61 (12)
O1—C5—C7—C8	177.84 (11)	C7—C5—O1—C4	75.09 (18)
C5—C7—C8—C7i	−0.99 (11)	C6—C5—O1—C4	−108.92 (13)

Symmetry code: (i) −x, y, −z+1/2.